Oxidative-Retinopathies: Female Neonate Rats Handle Bright Light Better Than Hyperoxia, Males React Strongly To Both

Abstract

Purpose: Exposure of neonatal rats to bright light or hyperoxia produce typical retinopathies [Light-Induced (LIR) and Oxygen-Induced (OIR)]. Given that Estrogen (E) was shown to act as a neuroprotective agent and that estrogen receptors were evidenced in the retina, the purpose of this study was to investigate if male and female retinas reacted differently in response to oxidative stress.

Methods: Newborn Sprague Dawley (SD) rats (N =15) were exposed to 80 ± 5% O2 + bright luminous environment of 750 lux (L + H group) between P4-P14. At P14, O2 was interrupted while light exposure continued until P28. A second group of rats were kept at room air with same light intensity from P4 to P28 (Light only group: L group). At P100, retinal function was investigated with the ERG. In parallel, we injected 17 β-Estradiol (4 and 12 µg, IP, daily from P6-P14) in SD pups exposed to postnatal hyperoxia from P8-P14. Experimental rats were subdivided as follows: Group 1 (G1: O2 + 4µg E; N = 8); Group 2 (G2: O2 + 12µg E; N = 8); Group 3 (G3: 4µg E; N = 8); Group 4 (G4: 12µg E; N = 8); Group 5 (G5: O2 only; N = 8); Group 6 (G6: control; N = 8). ERG were done at P30.

Results: ERG showed that female rats of the L group had scotopic a-and b waves and photopic b-wave amplitudes that were significantly higher than male [109 ± 41µV vs 52 ± 22 µV( P= 0.01); 398 ± 164 µV vs. 214 ± 85 µV (P=0.039) and 163 ± 53 µV vs. 72 ± 32 µV (P=0.006), respectively].No significant male-female differences noted in the L+H group. Females of the L+H group had significantly smaller scotopic (P=.01) and photopic (P=.002) b-waves compared to females of the L group. In males, only the photopic b-wave showed a similar effect (P=0.01). The latter results suggested that estrogen is detrimental to retinal function, a finding that was further confirm in the second experiment where we showed a significant (P<.01) reduction in ERG amplitudes (scotopic and photopic) in experimental rats receiving the highest dose of estrogen.

Conclusions: Our results reveal that in condition where the primary target of the oxidative stress is the outer retina (i.e. the photoreceptors) the female rats appear to be relatively better preserved than males. However, this sex advantage seems to be lost in situations where the inner retina (or retinal vasculature) as it is the case in OIR, presumably due to a detrimental effect of estrogen on retinal function.

Keywords: 510 electroretinography: non-clinical • 706 retinopathy of prematurity